title: New insights in the pathogenesis of multiple sclerosis--role of acrolein in neuronal and myelin damage.
abstract: Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) characterized by an inappropriate inflammatory reaction resulting in widespread myelin injury along white matter tracts. Neurological impairment as a result of the disease can be attributed to immune-mediated injury to myelin, axons and mitochondria, but the molecular mechanisms underlying the neuropathy remain incompletely understood. Incomplete mechanistic knowledge hinders the development of therapies capable of alleviating symptoms and slowing disease progression in the long-term. Recently, oxidative stress has been implicated as a key component of neural tissue damage prompting investigation of reactive oxygen species (ROS) scavengers as a potential therapeutic option. Despite the establishment of oxidative stress as a crucial process in MS development and progression, ROS scavengers have had limited success in animal studies which has prompted pursuit of an alternative target capable of curtailing oxidative stress. Acrolein, a toxic β-unsaturated aldehyde capable of initiating and perpetuating oxidative stress, has been suggested as a viable point of intervention to guide the development of new treatments. Sequestering acrolein using an FDA-approved compound, hydralazine, offers neuroprotection resulting in dampened symptom severity and slowed disease progression in experimental autoimmune encephalomyelitis (EAE) mice. These results provide promise for therapeutic development, indicating the possible utility of neutralizing acrolein to preserve and improve neurological function in MS patients.
authors.affiliation: Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA. riyi@purdue.edu.
authors.forename: Melissa
authors.initials: M
authors.lastname: Tully
authors.forename: Riyi
authors.initials: R
authors.lastname: Shi
mesh_terms: D000171:Acrolein / Q000494:pharmacology*; D000818:Animals; D002490:Central Nervous System / Q000187:drug effects* / Q000473:pathology*; D006801:Humans; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000473:pathology*; D009186:Myelin Sheath / Q000187:drug effects* / Q000473:pathology*; D018384:Oxidative Stress / Q000187:drug effects
chemical_list: D000171:Acrolein